Cumulative exposure risk

This policy seems to be rational and would be of tremendous help to registrants in getting more uses registered for their products. This would be especially useful when new uses (worth millions of dollars to the registrant) were to be added to the label in cases where no detectable residues were found in the food product and the risk cup (cumulative exposure risk) was nearly full. The following example highlights this point ... 

If workers are exposed simultaneously or successively to more than one chemical agent, the risk shall be assessed on the basis of the risk presented by all such chemical agents in combination. Usually, additive effects are assumed for the mixture of chemical agents, so the cumulative exposure is calculated as follows ... 

The odor perception threshold for benzene in water is 2 ing/L. The benzene drinking water unit risk is 8.3 x lO L/pg. Calculate the potential benzene intake rate (mg benzene/kg-d) and the cumulative cancer risk from drinking water with benzene concentrations at half of its odor threshold for a 30 year exposure duration. 

Up to 100 WLM of cumulative exposure, lung cancer risk shows... 

Two of the more interesting uses of pharmacokinetic data in risk assessment involve the neurotoxic agents lead and methylmercury (Chapter 4). In the case of lead, epidemiological studies have typically involved the development of quantitative relationships between levels of lead in the blood and adverse health effects. Other measures of lead in the body have also been used. Levels in blood are now very easy to measure, and they do carry the strong advantage that they integrate cumulative exposures from many possible sources (water, food, paint, soil, air, consumer products). Current public health targets for lead are expressed as blood concentrations, typically in pg/dL (Chapter 4). 

Let us assume that enough information is available regarding the levels of benzene in Mr. Z s well, the number of years he consumed the water, and even his water consumption rate, to derive a reasonably accurate estimate of his cumulative exposure from this source. The epidemiologists and biostatisticians carefully evaluate the dose-response data from the published epidemiology studies used as the basis for classifying benzene as a cause of leukemia. Further assume that we learn from this evaluation that Mr. Z incurred a cumulative benzene exposure approximately equivalent to the cumulative exposure that was found to cause a three-fold excess risk of leukemia in the occupational studies of benzene exposure. A relative risk of three. 

Of course if Mr. Z s cumulative exposure were found to be insufficient to at least double his normal background risk, he would fail to make his case that the corporation was to blame. 

The lARC has concluded that epidemiological studies have established the relationship between benzene exposure and the development of acute myelogenous leukemia and that there is sufficient evidence that benzene is carcinogenic to humans. Although a benzene-leukemia association has been made, the exact shape of the dose-response curve and/or the existence of a threshold for the response is unknown and has been the source of speculation and controversy. Some risk assessments suggest exponential increases in relative risk (of leukemias) with increasing cumulative exposure to benzene. At low levels of exposure, however, a small increase in leukemia mortality cannot be distinguished from a no-risk situation. In addition to cumulative dose other factors such as multiple solvent exposure, familial connection, and individual sus-... 

A case-cohort study of aluminum production plant workers showed a clear excess of lung cancer risk in men who had worked in Soder-berg potrooms in jobs with high exposure to CTPV, and that the risk was not due to confounding by smoking. The rate ratio for lung cancer rose with cumulative exposure to CTPV measured as benzene-soluble material to 2.25 at 10-19 mg/m -years benzene-soluble matter but did not rise with further exposure. 

One cohort study of workers in the United States who manufactured 1,3-butadiene monomer showed a moderate and significant excess of lymphohaematopoietic cancers based on 42 deaths. Persons employed before 1950 were especially at increased risk, but there was no convincing association with a cumulative exposure score. A total of... 

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